甲基化芯片技术检测粪便DNA甲基化在海南地区少数民族人群大肠癌筛查中的应用

Application of methylation microarrays in detection of fecal DNA methylation in colorectal cancer screening among ethnic minority populations in Hainan

摘要:

目的 分析甲基化芯片技术检测粪便DNA甲基化在海南地区少数民族人群大肠癌筛查中的应用价值。方法 选取2020年6月—2022年6月海南省人民医院就诊的大肠癌高危少数民族人群102例。另选取同期该院招募的30例健康志愿者作为对照组。留取所有患者在结肠镜检查前自然排出或服用泻药后的第一段粪便，通过甲基化芯片技术检测粪便DNA甲基化。根据肠镜病理检查结果，将102例患者分为大肠癌组、腺瘤组、增生性息肉组。对比4组粪便DNA中VAV3、IKZF1、RIMS1基因甲基化状态。将肠镜病理检查结果作为金标准，评估粪便DNA中VAV3、IKZF1、RIMS1基因联合检测大肠癌、腺瘤的诊断效能。结果 大肠癌组VAV3、IKZF1、RIMS1基因单独及联合检测甲基化率高于腺瘤组、增生性息肉组、对照组（P <0.05）。腺瘤组与增生性息肉组VAV3、IKZF1、RIMS1基因单独及联合检测甲基化率比较，差异无统计学意义（P >0.05）。VAV3、IKZF1、RIMS1基因联合检测大肠癌的特异性、敏感性、阴性预测值、阳性预测值、准确率最高，分别为100.00%、92.31%、92.59%、100.00%和96.08%。粪便DNA中VAV3、IKZF1、RIMS1基因联合检测腺瘤的特异性、敏感性、阴性预测值、阳性预测值、准确率最高，分别为97.30%、71.43%、90.00%、90.91%和90.20%。结论 海南地区少数民族人群大肠癌患者粪便DNA中VAV3、IKZF1、RIMS1基因表现出较高的甲基化水平，且3个基因联合检测可提升大肠癌、腺瘤的诊断效能。

Abstract:

Objective To analyze the value of fecal DNA methylation detected by methylation microarrays in colorectal cancer screening among ethnic minority populations in Hainan.Methods A total of 102 ethnic minority individuals at a high risk for colorectal cancer in Hainan Provincial People's Hospital from June 2020 to June 2022 were selected, and another 30 healthy volunteers were recruited as the control group. The forepart feces samples of all patients excreted naturally or facilitated with laxatives before colonoscopy were collected for DNA methylation profiling via microarrays. According to the pathological findings, 102 patients were divided into colorectal cancer group, adenoma group and hyperplastic polyp group, and the methylation levels of VAV3, IKZF1 and RIMS1 genes in feces samples of the four groups were compared. Taking the pathological findings as the gold standard, we evaluated the diagnostic efficacy of the combined detection of fecal VAV3, IKZF1 and RIMS1 genes for colorectal cancer and adenoma.Results The methylation levels of fecal VAV3, IKZF1 and RIMS1 genes and their combination in the colorectal cancer group were higher than those in the adenoma group, hyperplastic polyp group and control group (P < 0.05). There was no significant difference in the methylation levels of fecal VAV3, IKZF1 and RIMS1 genes and their combination between adenoma group and hyperplastic polyp group (P > 0.05). The combined detection of fecal VAV3, IKZF1 and RIMS1 genes yielded the highest specificity, sensitivity, negative predictive value, positive predictive value, and accuracy for diagnosing colorectal cancer and adenoma, with them being 100.00%, 92.31%, 92.59%, 100.00%, and 96.08% for colorectal cancer, and 97.30%, 71.43%, 90.00%, 90.91%, and 90.20% for adenoma, respectively.Conclusions The DNA methylation profiling via microarrays indicates that the VAV3, IKZF1 and RIMS1 genes in the feces of colorectal cancer patients of ethnic minority in Hainan are highly methylated. The combined detection of the three genes can improve the diagnostic efficacy of colorectal cancer and adenoma.